Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accou...Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.展开更多
目的探讨METTL14通过调控巨噬细胞分化抑制宫颈癌病理性发展及相关机制。方法检测宫颈癌病变样本METTL14 m RNA和蛋白,以及IL-6、iNOS、Arg-1和CD206表达变化。PMA诱导THP-1细胞转化为巨噬细胞,慢病毒过表达或抑制METTL14表达,检测IL-6...目的探讨METTL14通过调控巨噬细胞分化抑制宫颈癌病理性发展及相关机制。方法检测宫颈癌病变样本METTL14 m RNA和蛋白,以及IL-6、iNOS、Arg-1和CD206表达变化。PMA诱导THP-1细胞转化为巨噬细胞,慢病毒过表达或抑制METTL14表达,检测IL-6、iNO、Arg-1和CD206表达变化以及PI3K/AKT/GSK3β/β-catenin信号通路相关蛋白表达情况。随后加入PI3K/AKT/GSK3β/β-catenin信号通路激动剂和抑制剂,检测过表达或抑制METTL14后,巨噬细胞IL-6、iNO、Arg-1和CD206表达变化,并取其上清制成条件培养基,孵育Hela细胞,检测细胞凋亡和增殖情况。结果1)宫颈癌病变组织中METTL14 mRNA和蛋白表达降低(P<0.05),巨噬细胞M1型标志物IL-6和iNOS表达明显降低(P<0.05),而M2型标志物Arg-1和CD206表达明显升高(P<0.05)。2)巨噬细胞过表达METTL14后,IL-6和iNOS表达明显升高(P<0.05),而Arg-1和CD206表达明显降低(P<0.05),M1/M2比例升高;抑制METTL14表达后,M1型标志物降低(P<0.05),M2型标志物升高(P<0.05),M1/M2比例降低。3)巨噬细胞中转染OE-METTL14慢病毒组PI3K/AKT/GSK3β/β-catenin信号通路被抑制(P<0.05);加入PI3K/AKT激动剂后,M1型标志物降低而M2型标记物升高(P<0.05),M1/M2比例降低;OE-METTL14可逆转此趋势。Sh-METTL14慢病毒组PI3K/AKT/GSK3β/β-catenin信号通路被激活(P<0.05),加入PI3K/AKT抑制剂后,M1型标志物升高而M2型标记物降低(P<0.05),M1/M2比例升高;Sh-METTL14可逆转此趋势。4)取转染OE-METTL14慢病毒后的巨噬细胞上清培养Hela细胞,可见细胞凋亡明显增多(P<0.05),增殖明显减少(P<0.05)。Sh-METTL14组的Hela细胞则表现出细胞凋亡减少(P<0.05),增殖增多(P<0.05)。结论METTL14通过PI3K/AKT/GSK3β/β-catenin信号通路调控巨噬细胞分化可能有促进宫颈癌细胞凋亡,抑制增殖的作用。展开更多
目的:单核巨噬细胞系统参与先天性及适应性免疫应答,并具有极强的可塑性,对于肝损伤中的炎症反应、促进组织修复方面起着重要作用。本研究旨在探讨药物性肝损伤(drug-induced liver injury,DILI)患者外周血单核细胞百分比升高与疾病严...目的:单核巨噬细胞系统参与先天性及适应性免疫应答,并具有极强的可塑性,对于肝损伤中的炎症反应、促进组织修复方面起着重要作用。本研究旨在探讨药物性肝损伤(drug-induced liver injury,DILI)患者外周血单核细胞百分比升高与疾病严重程度的相关性,并进一步检测外周血中单核细胞M1、M2亚型的水平。方法:收集170例DILI患者(分为轻中度组49例,重度及以上组121例)和100例健康体检人群(对照组)的临床资料。对3组研究对象的临床资料进行组间比较,对DILI患者单核细胞百分比、淋巴细胞百分比及淋巴细胞百分比与单核细胞百分比比值(ratio of lymphocytes to monocytes,LMR)与肝功能临床参数行相关性分析。同时收集10例健康人和13例DILI患者入院时(治疗前)及治疗2周后的清晨空腹肘静脉血,采用流式细胞术检测外周血单核细胞表面CD86(M1型单核细胞)、CD163(M2型单核细胞)的表达。结果:DILI患者单核细胞百分比与总胆红素(total bilirubin,TBil)水平呈正相关(r=0.512,P<0.01);LMR、淋巴细胞百分比与TBil水平均呈负相关(r=−0.499、r=−0.259,均P<0.01);流式细胞术结果显示:与对照组比较,DILI组患者外周血M1型单核细胞显著增加(P<0.001),M2型单核细胞减少(P=0.036),M2/M1比值显著降低(P=0.011);DILI组患者治疗前后,随着肝功能好转,M1、M2型单核细胞变化趋势发生逆转,M2/M1比值升高(P=0.034)。结论:DILI患者外周血单核细胞百分比升高、LMR降低与肝损伤严重程度有关。此外,在肝损伤进展阶段以M1型单核细胞增加为主,随着肝功能的改善,M2型单核细胞逐渐恢复。因此,靶向调控单核/巨噬细胞M1、M2极化可能作为未来治疗DILI的新策略。展开更多
The Internet of things(IoT)has become a key infrastructure providing up-to-date and fresh information for policy analysis and decision-making of upper-layer applications.However,there are limited sensing and communica...The Internet of things(IoT)has become a key infrastructure providing up-to-date and fresh information for policy analysis and decision-making of upper-layer applications.However,there are limited sensing and communication resources in IoT devices,which significantly affects the timeliness and freshness of the updated status.This work proposes two schemes,namely,the generation rate control and service rate reservation schemes,to improve the overall information freshness of multiple status update streams at the receiver.Specifically,using the recently proposed Age of Information(AoI)as the metric for evaluating information freshness,we characterized the overall information freshness,i.e.,the overall average AoI at the receiver for both schemes,by considering the urgency difference of status update and streams.Both schemes for status updates and streams,respectively,were formulated as two optimization problems.We proved that both problems are convex and the optimal generation and service rates for different streams are found by the standard convex optimization algorithm.Moreover,we proposed both approximate optimal generation and approximate optimal service rate for fast deployment in heavy and light load cases.Numerical results verify the theoretical findings and accuracy of the proposed approximate solutions,guiding the design and deployment of IoT.展开更多
文摘Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.
文摘目的探讨METTL14通过调控巨噬细胞分化抑制宫颈癌病理性发展及相关机制。方法检测宫颈癌病变样本METTL14 m RNA和蛋白,以及IL-6、iNOS、Arg-1和CD206表达变化。PMA诱导THP-1细胞转化为巨噬细胞,慢病毒过表达或抑制METTL14表达,检测IL-6、iNO、Arg-1和CD206表达变化以及PI3K/AKT/GSK3β/β-catenin信号通路相关蛋白表达情况。随后加入PI3K/AKT/GSK3β/β-catenin信号通路激动剂和抑制剂,检测过表达或抑制METTL14后,巨噬细胞IL-6、iNO、Arg-1和CD206表达变化,并取其上清制成条件培养基,孵育Hela细胞,检测细胞凋亡和增殖情况。结果1)宫颈癌病变组织中METTL14 mRNA和蛋白表达降低(P<0.05),巨噬细胞M1型标志物IL-6和iNOS表达明显降低(P<0.05),而M2型标志物Arg-1和CD206表达明显升高(P<0.05)。2)巨噬细胞过表达METTL14后,IL-6和iNOS表达明显升高(P<0.05),而Arg-1和CD206表达明显降低(P<0.05),M1/M2比例升高;抑制METTL14表达后,M1型标志物降低(P<0.05),M2型标志物升高(P<0.05),M1/M2比例降低。3)巨噬细胞中转染OE-METTL14慢病毒组PI3K/AKT/GSK3β/β-catenin信号通路被抑制(P<0.05);加入PI3K/AKT激动剂后,M1型标志物降低而M2型标记物升高(P<0.05),M1/M2比例降低;OE-METTL14可逆转此趋势。Sh-METTL14慢病毒组PI3K/AKT/GSK3β/β-catenin信号通路被激活(P<0.05),加入PI3K/AKT抑制剂后,M1型标志物升高而M2型标记物降低(P<0.05),M1/M2比例升高;Sh-METTL14可逆转此趋势。4)取转染OE-METTL14慢病毒后的巨噬细胞上清培养Hela细胞,可见细胞凋亡明显增多(P<0.05),增殖明显减少(P<0.05)。Sh-METTL14组的Hela细胞则表现出细胞凋亡减少(P<0.05),增殖增多(P<0.05)。结论METTL14通过PI3K/AKT/GSK3β/β-catenin信号通路调控巨噬细胞分化可能有促进宫颈癌细胞凋亡,抑制增殖的作用。
文摘目的:单核巨噬细胞系统参与先天性及适应性免疫应答,并具有极强的可塑性,对于肝损伤中的炎症反应、促进组织修复方面起着重要作用。本研究旨在探讨药物性肝损伤(drug-induced liver injury,DILI)患者外周血单核细胞百分比升高与疾病严重程度的相关性,并进一步检测外周血中单核细胞M1、M2亚型的水平。方法:收集170例DILI患者(分为轻中度组49例,重度及以上组121例)和100例健康体检人群(对照组)的临床资料。对3组研究对象的临床资料进行组间比较,对DILI患者单核细胞百分比、淋巴细胞百分比及淋巴细胞百分比与单核细胞百分比比值(ratio of lymphocytes to monocytes,LMR)与肝功能临床参数行相关性分析。同时收集10例健康人和13例DILI患者入院时(治疗前)及治疗2周后的清晨空腹肘静脉血,采用流式细胞术检测外周血单核细胞表面CD86(M1型单核细胞)、CD163(M2型单核细胞)的表达。结果:DILI患者单核细胞百分比与总胆红素(total bilirubin,TBil)水平呈正相关(r=0.512,P<0.01);LMR、淋巴细胞百分比与TBil水平均呈负相关(r=−0.499、r=−0.259,均P<0.01);流式细胞术结果显示:与对照组比较,DILI组患者外周血M1型单核细胞显著增加(P<0.001),M2型单核细胞减少(P=0.036),M2/M1比值显著降低(P=0.011);DILI组患者治疗前后,随着肝功能好转,M1、M2型单核细胞变化趋势发生逆转,M2/M1比值升高(P=0.034)。结论:DILI患者外周血单核细胞百分比升高、LMR降低与肝损伤严重程度有关。此外,在肝损伤进展阶段以M1型单核细胞增加为主,随着肝功能的改善,M2型单核细胞逐渐恢复。因此,靶向调控单核/巨噬细胞M1、M2极化可能作为未来治疗DILI的新策略。
基金sponsored by the National Natural Science Foundation of China under Grant 61901066,Grant 61971077sponsored by Natural Science Foundation of Chongqing,China under Grant cstc2019jcyjmsxmX0575,Grant cstc2021jcyj-msxmX0458+2 种基金in part by the Entrepreneurship and Innovation Support Plan of Chongqing for Returned Overseas Scholars under Grant cx2021092supported by the open research fund of National Mobile Communications Research Laboratory,Southeast University(No.2021D13,No.2022D06)the Industrial Internet innovation and development project(No.TC200A00M).
文摘The Internet of things(IoT)has become a key infrastructure providing up-to-date and fresh information for policy analysis and decision-making of upper-layer applications.However,there are limited sensing and communication resources in IoT devices,which significantly affects the timeliness and freshness of the updated status.This work proposes two schemes,namely,the generation rate control and service rate reservation schemes,to improve the overall information freshness of multiple status update streams at the receiver.Specifically,using the recently proposed Age of Information(AoI)as the metric for evaluating information freshness,we characterized the overall information freshness,i.e.,the overall average AoI at the receiver for both schemes,by considering the urgency difference of status update and streams.Both schemes for status updates and streams,respectively,were formulated as two optimization problems.We proved that both problems are convex and the optimal generation and service rates for different streams are found by the standard convex optimization algorithm.Moreover,we proposed both approximate optimal generation and approximate optimal service rate for fast deployment in heavy and light load cases.Numerical results verify the theoretical findings and accuracy of the proposed approximate solutions,guiding the design and deployment of IoT.
